There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Retrospective study: The diagnostic accuracy of conventional forceps biopsy of gastric epithelial compared to endoscopic submucosal dissection (STROBE compliant).

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

PL02-05 

All cancers are due to abnormalities in DNA. The availability of the human genome sequence has led to the proposal that resequencing of cancer genomes will reveal the full complement of somatic mutations and hence all the cancer genes. To explore the nature of the information that will be derived from cancer genome sequencing we have sequenced the coding exons of the family of 518 protein kinases, ~1.3Mb DNA per cancer sample, in 210 cancers of diverse histological types. Despite the screen being directed toward the coding regions of a gene family that has previously been strongly implicated in oncogenesis, the results indicate that the majority of somatic mutations detected are “passengers”. There is considerable variation in the number and pattern of these mutations between individual cancers, indicating substantial diversity of processes of molecular evolution between cancers. The imprints of exogenous mutagenic exposures, mutagenic treatment regimes and DNA repair defects can all be seen in the distinctive mutational signatures of individual cancers. This systematic mutation screen and others have previously yielded a number of cancer genes that are frequently mutated in one or more cancer types and which are now anticancer drug targets (for example BRAF , PIK3CA , and EGFR ). However, detailed analyses of the data from our screen additionally suggest that there exist a large number of additional “driver” mutations which are distributed across a substantial number of genes. It therefore appears that cells may be able to utilise mutations in a large repertoire of potential cancer genes to acquire the neoplastic phenotype. However, many of these genes are employed only infrequently. These findings may have implications for future anticancer drug development.

Patterns of Somatic Mutation in Human Cancer Genomes

The hepatic stellate cell has surprised and engaged physiologists, pathologists, and hepatologists for over 130 years, yet clear evidence of its role in hepatic injury and fibrosis only emerged following the refinement of methods for its isolation and characterization. The paradigm in liver injury of activation of quiescent vitamin A-rich stellate cells into proliferative, contractile, and fibrogenic myofibroblasts has launched an era of astonishing progress in understanding the mechanistic basis of hepatic fibrosis progression and regression. But this simple paradigm has now yielded to a remarkably broad appreciation of the cell's functions not only in liver injury, but also in hepatic development, regeneration, xenobiotic responses, intermediary metabolism, and immunoregulation. Among the most exciting prospects is that stellate cells are essential for hepatic progenitor cell amplification and differentiation. Equally intriguing is the remarkable plasticity of stellate cells, not only in their variable intermediate filament phenotype, but also in their functions. Stellate cells can be viewed as the nexus in a complex sinusoidal milieu that requires tightly regulated autocrine and paracrine cross-talk, rapid responses to evolving extracellular matrix content, and exquisite responsiveness to the metabolic needs imposed by liver growth and repair. Moreover, roles vital to systemic homeostasis include their storage and mobilization of retinoids, their emerging capacity for antigen presentation and induction of tolerance, as well as their emerging relationship to bone marrow-derived cells. As interest in this cell type intensifies, more surprises and mysteries are sure to unfold that will ultimately benefit our understanding of liver physiology and the diagnosis and treatment of liver disease.

/pdf/hepatic-stellate-cells-protean-multifunctional-and-enigmatic-1ctrvjmfhn.pdf

Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

Integrative Genomics Viewer

Background Brain metastasis is extremely rare but predicts dismal prognosis in papillary thyroid cancer (PTC). Dynamic evaluation of stepwise metastatic lesions was barely conducted to identify the longitudinal genomic evolution of brain metastasis in PTC. Method Chronologically resected specimen was analyzed by whole exome sequencing, including four metastatic lymph nodes (lyn 1-4) and brain metastasis lesion (BM). Phylogenetic tree was reconstructed to infer the metastatic pattern and the potential functional mutations. Results Contrasting with lyn1, ipsilateral metastatic lesions (lyn2-4 and BM) with shared biallelic mutations of TSC2 indicated different genetic originations from multifocal tumors. Lyn 3/4, particularly lyn4 exhibited high genetic similarity with BM. Besides the similar mutational compositions and signatures, shared functional mutations (CDK4 R24C , TP53R342*) were observed in lyn3/4 and BM. Frequencies of these mutations gradually increase along with the metastasis progression. Consistently, TP53 knockout and CDK4 R24C introduction in PTC cells significantly decreased radioiodine uptake and increased metastatic ability. Conclusion Genomic mutations in CDK4 and TP53 during the tumor evolution may contribute to the lymph node and brain metastasis of PTC.

/pdf/longitudinal-genomic-evolution-of-conventional-papillary-28vadbyhws.pdf

Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis.

SKLB70326, a novel small-molecule inhibitor of cell-cycle progression, induces G0/G1 phase arrest and apoptosis in human hepatic carcinoma cells

A universal anti-thrombotic and antibacterial coating: a chemical approach directed by Fenton reaction and silane coupling

Objective To evaluate the therapeutical effect of endostatin adenoviral vector on malignant ascites and compare it with the combined effect of ad-endostatin and DDP. Methods We transfected SKOV3 cells with ad-endostatin to inhibit human umbilical vein endothelial cells (HUVEC) proliferation. Then we administered ad-endostatin intraperitoneally in BALB/c mice to detect the serum endostatin expression and in the mice with malignant ascites to evaluate the therapeutic efficacy. Results Recombinant endostatin inhibited HUVEC proliferation. Endostatin was expressed in serum after intraperitoneal injection of ad-endostatin. The effects of endostatin on inhibition of the ascites accumulation and peritoneal capillary permeability, on demotion of VEGF protein level and microvascular density in tumor tissues, on reduction of the number of red cells and tumor cells counted in malignant ascites, and on prolongation of mice survival were significant in two different malignant ascites. Furthermore, the combination of ad-endostatin with DDP increased the therapeutic efficacy. Conclusion These data suggested that endostatin gene therapy may represent a potential new treatment for malignant ascites, and the therapeutic efficacy can be enhanced by a combination of ad-endostatin with chemotherapy.

Inhibition of malignant ascites with endostatin adenoviral vector

Objective To investigate severity of gastrointestinal symptoms, quality of life, and mental health status of patients with irritable bowel syndrome (IBS) and functional dyspepsia (FD). Methods IBS patients were enrolled consecutively at the Outpatient Department of Gastroenterology, West China Hospital, Sichuan University from September 2012 to May 2013. The participants were divided into two groups according to their appearance with FD. Ten healthy volunteers served as normal controls. A questionnaire survey was undertaken to measure scores of gastrointestinal symptom rating scale (GSRS), Chinese IBS-quality of life (ChIBS-QOL), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) and medical conditions. Results Twenty-five (41.7%) IBS patients were overlapped with FD (IBS-FD). The IBS-FD patients had significantly higher scores of GSRS than IBS patients and healthy volunteers (P<0.05). The IBS-FD patients saw doctors more frequently than IBS patients (P<0.05). Neither anxiety nor depression were observed in healthy volunteers. The IBS patients were more likely to present mild anxiety and depression, while the IBS-FD patients were more likely to present moderate to severe anxiety and depression. The IBS-FD patients had significantly higher prevalence of anxiety and depression than IBS patients (80.0% vs. 51.4%, 76.0% vs. 48.6% respectively, P<0.05). Scores of GSRS, ChIBS-QOL and prevalence of anxiety and depression were the highest in the IBS-FD patients with constipation (IBS-C-FD, P<0.05). Conclusion IBS-FD patients especially those with constipation suffer more gastrointestinal discomforts, and are more likely to suffer from anxiety and depression and poor quality of life compared with those with IBS only.

Li Yang

Papers

Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis.

SKLB70326, a novel small-molecule inhibitor of cell-cycle progression, induces G0/G1 phase arrest and apoptosis in human hepatic carcinoma cells

A universal anti-thrombotic and antibacterial coating: a chemical approach directed by Fenton reaction and silane coupling

Inhibition of malignant ascites with endostatin adenoviral vector

[Clinical features, quality of life and psychological health of patients with irritable bowel syndrome and functional dyspepsia].